1.1.1.39: malate dehydrogenase (decarboxylating)

This is an abbreviated version, for detailed information about malate dehydrogenase (decarboxylating), go to the full flat file.

Reaction

(S)-malate
+
NAD+
=
pyruvate
+
CO2
+
NADH

Synonyms

AZC3656 protein, dehydrogenase, malate, diphosphate nucleotide dependent malic enzyme, DMA, DME, m-NAD-ME, malic enzyme, malic enzyme 2, malic enzyme-NAD, ME, ME-NAD, ME2, mitochondrial malic enzyme, mitochondrial NAD(P)+-dependent malic enzyme, mitochondrial NAD+-dependent malic enzyme, mitochondrial NAD-malic enzyme, NAD(P)+-malic enzyme, NAD+-dependent malic enzyme, NAD-dependent malic enzyme, NAD-malic enzyme, NAD-ME, NAD-ME1, NAD-ME2, NAD-MEH, NAD-preferring malic enzyme, NAD-preferring ME, NAD-specific malic enzyme, pyruvic-malic carboxylase

ECTree

     1 Oxidoreductases
         1.1 Acting on the CH-OH group of donors
             1.1.1 With NAD+ or NADP+ as acceptor
                1.1.1.39 malate dehydrogenase (decarboxylating)

Engineering

Engineering on EC 1.1.1.39 - malate dehydrogenase (decarboxylating)

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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
K143A
-
site-directed mutagenesis, malate binding residue, mutant shows highly increased kcat for malate and fumarate compared to the wild-type enzyme
K362H
-
the mutant enzyme displays a considerable elevation in Km for NADP+, and the kcat for NAD+ value is elevated compared to the wild-type enzyme
N434A
-
site-directed mutagenesis, the interaction of the 434 position residue with malate is lost in the mutant, causing malate to reorient itself, leading to a slower decarboxylation
N434E
-
site-directed mutagenesis, the longer glutamine side chain sticks into the active site and causes a change in the position of malate and/or NAD+ resulting in more than a 10000fold decrease in V/Et for the mutant enzyme compared to the wild-type enzyme
N434M
-
site-directed mutagenesis, the longer methionine side chain sticks into the active site and causes a change in the position of malate and/or NAD+ resulting in more than a 10000fold decrease in V/Et for the mutant enzyme compared to the wild-type enzyme
N479Q
-
site-directed mutagenesis, the stepwise oxidative decarboxylation mechanism observed for the wild-type enzyme changed to a concerted one, which is totally rate limiting, for the N479Q mutant enzyme
N479S
-
site-directed mutagenesis, the mutant with the shorter serine side chain shows very similar values of KNAD+, Kmalate, and isotope effects relative to the wild-type enzyme, but V/Et is decreased 2000fold due to an increased freedom of rotation, resulting in nonproductively bound cofactor
R105A
-
site-directed mutagenesis, fumarate binding residue, mutant shows 7-8fold reduced initial velocity with malate and Mg2+ compared to the wild-type enzyme, and is no longer activated by fumarate and malate
R181K
-
site-directed mutagenesis, the mutant shows a 100fold increase in the Km for malate, a 30fold increase in the Ki for oxalate, and a 10fold increase in Ki for NADH, but only a slight or no change in KNAD compared to the wild-type enzyme
R181Q
-
site-directed mutagenesis, the mutant shows a 100fold increase in the Km for malate, a 30fold increase in the Ki for oxalate, and a 10fold increase in Ki for NADH, but only a slight or no change in KNAD compared to the wild-type enzyme. The activity of the R181Q mutant can be partially rescued by ammonium ion likely by binding in the pocket vacated by the guanidinium group of R181
S433A
-
site-directed mutagenesis, KNAD+ for the S433A mutant enzyme is increased by 80fold compared to the wild-type enzyme
S433C
-
site-directed mutagenesis, the mutant enzyme exhibits 9fold and 500fold increases in Kmalate and KNAD, respectively, compared to the wild-type enzyme
additional information